Thymidine synthesized de novo by monolayers of macrophages has been found to be an inhibitor of DNA synthesis and cell proliferation. It is now intended to extend these studies and investigate whether other nucleosides are also synthesized and secreted by macrophages in culture. For this purpose, macrophage monolayers will be pulsed with precursors of nucleoside metabolism and supernatants analyzed by two-dimensional thin layer chromatography. The secretory process will be studied under various conditions of macrophage activation and with cells at different stages of differentiation. The effect of phagocytosis will be determined. The relationship of the secretory phenomenon to the phase of the cell cycle will be studied. Macrophages will be stimulated to divide with fibroblast-conditioned media and the induction of DNA synthesis will be correlated with the expression of thymidine kinase. The role of nucleoside kinases in preventing the secretion of nucleosides will be explored. The functional significance of thymidine secretion by macrophages will be explored as a possible contributory mechanism of tumor cell growth control. This will involve the determination of whether the in vivo regression of animal and human tumors infiltrated by macrophages is correlated with their in vitro sensitivity to thymidine-mediated cytostasis.